Cancer chemotherapy resistance: Mechanisms and recent breakthrough in targeted drug delivery

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 958, P. 176013 - 176013

Published: Aug. 24, 2023

Language: Английский

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Role of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinoma

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Feb. 10, 2023

Abstract Emerging evidence showed that epigenetic regulation plays important role in the pathogenesis of HCC. N 4-acetocytidine (ac4C) was an acetylation chemical modification mRNA, and NAT10 is reported to regulate ac4C enhance endoplasmic reticulum stress (ERS) tumor metastasis. Here, we report a novel mechanism by which NAT10-mediated mRNA ac4C-modified HSP90AA1 regulates metastasis resistance ERS Immunohistochemical, bioinformatics analyses, vitro vivo experiments, e.g., acRIP-Seq, RNA-Seq, double luciferase reporter experiment, were employed investigate effect on drug The increased expression associated with HCC risk poor prognosis. Cell animal experiments enhanced ability apoptosis cells state. could upregulate level ac4C, maintain stability HSP90AA1, further promotes hepatoma Lenvatinib. This study proposes In addition, demonstrated regulatory NAT10-HSP90AA1 cells.

Language: Английский

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Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer

Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)

Published: March 20, 2024

Abstract The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads stress (ER stress). As ER ensues, protein response (UPR), comprising three signaling pathways—inositol-requiring enzyme 1, kinase R-like kinase, activating transcription factor 6 promptly activates enhance ER’s protein-folding capacity restore homeostasis. However, prolonged levels propels UPR towards cellular demise subsequent inflammatory cascade, contributing development human diseases, including cancer, neurodegenerative disorders, diabetes. Notably, increased expression all pathways has been observed in these pathologies, reduction molecule correlates with decreased proliferation disease-associated target cells. Consequently, therapeutic strategies targeting stress-related interventions have attracted significant research interest. In this review, we elucidate critical role metabolic, offering novel approaches for conditions.

Language: Английский

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Autophagy and the unfolded protein response shape the non-alcoholic fatty liver landscape: decoding the labyrinth

Metabolism, Journal Year: 2024, Volume and Issue: 154, P. 155811 - 155811

Published: Feb. 2, 2024

Language: Английский

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Exploring the intricacies of calcium dysregulation in ischemic stroke: Insights into neuronal cell death and therapeutic strategies

Life Sciences, Journal Year: 2024, Volume and Issue: 347, P. 122651 - 122651

Published: April 19, 2024

Language: Английский

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Epitranscriptomics and epiproteomics in cancer drug resistance: therapeutic implications

Signal Transduction and Targeted Therapy, Journal Year: 2020, Volume and Issue: 5(1)

Published: Sept. 8, 2020

Abstract Drug resistance is a major hurdle in cancer treatment and key cause of poor prognosis. Epitranscriptomics epiproteomics are crucial cell proliferation, migration, invasion, epithelial–mesenchymal transition. In recent years, epitranscriptomic epiproteomic modification has been investigated on their roles overcoming drug resistance. this review article, we summarized the progress three novel aspects: (i) mRNA modification, which includes alternative splicing, A-to-I methylation; (ii) noncoding RNAs involves miRNAs, lncRNAs, circRNAs; (iii) posttranslational molecules encompasses inactivation/efflux, target modifications, DNA damage repair, death resistance, EMT, metastasis. addition, discussed therapeutic implications targeting some classical chemotherapeutic drugs such as cisplatin, 5-fluorouridine, gefitinib via these modifications. Taken together, highlights importance provides new insights potential targets to reverse

Language: Английский

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Connections between endoplasmic reticulum stress-associated unfolded protein response, mitochondria, and autophagy in arsenic-induced carcinogenesis

Seminars in Cancer Biology, Journal Year: 2021, Volume and Issue: 76, P. 258 - 266

Published: April 6, 2021

Arsenic exposure in contaminated drinking water is a global health issue, as more than 200 million people are affected globally. has been known to cause skin, liver, lung, bladder and prostate cancers. Accordingly, it categorized group I human carcinogen by the International Agency for Research on Cancer (IARC). Various natural anthropogenic activities lead release of arsenic environment, contaminating air, food sources. Traditionally, genetic mutations have center cancer research. However, emerging studies now focused importance epigenetics, metabolism endoplasmic reticulum (ER) stress cancer. highly capable inducing cells via generation free radicals causing oxidative stress, epigenetic alterations, mitochondrial dysfunction, activation intracellular signaling pathways, impairment autophagy DNA repair systems. The able utilize unfolded protein response (UPR) overcome these internal stresses various stages arsenic-induced carcinogenesis, from growth immune responses. UPR an evolutionarily conserved that both survival apoptotic outcomes. PERK, IRE1α ATF6α three ER sensors activated maintain cellular proteostasis, which can also promote apoptosis prolonged stress. dual nature different types challenge researchers. We must investigate role connections among stress-associated UPR, dysfunction malignancies identify key targets prevention therapeutics.

Language: Английский

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Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

Biomolecules, Journal Year: 2021, Volume and Issue: 11(2), P. 135 - 135

Published: Jan. 21, 2021

Autophagy, which is a conserved biological process and essential mechanism in maintaining homeostasis metabolic balance, enables cells to degrade cytoplasmic constituents through lysosomes, recycle nutrients, survive during starvation. Autophagy exerts an anticarcinogenic role normal inhibits the malignant transformation of cells. On other hand, aberrations autophagy are involved gene derangements, cell metabolism, tumor immune surveillance, invasion metastasis, drug-resistance. Therefore, autophagy-targeted drugs may function as anti-tumor agents. Accumulating evidence suggests that flavonoids have properties, including those relating cellular proliferation inhibition, induction apoptosis, autophagy, necrosis, cycle arrest, senescence, impairment migration, invasion, angiogenesis, reduction multidrug resistance Flavonoids, group natural polyphenolic compounds characterized by multiple targets participate pathways, been widely studied different models for modulation. However, flavonoid-induced commonly interacts with mechanisms, comprehensively influencing anticancer effect. Accordingly, targeted become core treatment tumors. This paper reviews their interaction so provide comprehensive in-depth account on how exert tumor-suppressive effects autophagy.

Language: Английский

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Role of Medicinal plant‐derived Nutraceuticals as a potential target for the treatment of breast cancer

Journal of Food Biochemistry, Journal Year: 2022, Volume and Issue: 46(12)

Published: Sept. 19, 2022

Breast cancer (BC) is one of the most challenging cancers to treat, accounting for many cancer-related deaths. Over some years, chemotherapy, hormone treatment, radiation, and surgeries have been used treat cancer. Unfortunately, these treatment options are unsuccessful due crucial adverse reactions multidrug tolerance/resistance. Although it clear that substances in nutraceuticals category a lot anti-cancer activity, using supplementary therapy strategy, this case, could be very beneficial. Nutraceuticals therapeutic agents, which nutrients drug-like characteristics can diseases. Plant categorized into polyphenols, terpenoids, vitamins, alkaloids, flavonoids part health food products, great potential combating BC. reduce BC's severity, limit malignant cell growth, modify mechanisms. acting by attenuating Hedgehog, Nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB), Notch, Wnt/β-catenin signaling main pathways controlling self-renewal breast stem (BCSCs). This article reviews important their modes action, powerful versus Practical applications Nutraceuticals' importance control diagnosis undeniable cannot overlooked. Natural dietary compounds wide range uses traditional medicine. In addition, natural chemicals enhance effectiveness other medicines. They may also as process independently because capacity affect several pathways. study highlights variety chemicals, mechanisms routes, synergistic effects, future potentials all examined.

Language: Английский

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Loss of PERK function promotes ferroptosis by downregulating SLC7A11 (System Xc⁻) in colorectal cancer

Redox Biology, Journal Year: 2023, Volume and Issue: 65, P. 102833 - 102833

Published: July 29, 2023

Ferroptosis, a genetically and biochemically distinct form of programmed cell death, is characterised by an iron-dependent accumulation lipid peroxides. Therapy-resistant tumor cells display vulnerability toward ferroptosis. Endoplasmic Reticulum (ER) stress Unfolded Protein Response (UPR) play critical role in cancer to become therapy resistant. Tweaking the balance UPR make susceptible ferroptotic death could be attractive therapeutic strategy. To decipher emerging contribution ER process, we observe that ferroptosis inducer RSL3 promotes (PERK, ATF6, IRE1α), along with overexpression cystine-glutamate transporter SLC7A11 (System Xc-). Exploring particular arm modulating expression subsequent ferroptosis, notice PERK selectively inducing colorectal carcinoma. inhibition reduces ATF4 recruitment promoter results its downregulation. Loss function not only primes for increased peroxidation but also limits vivo growth, demonstrating active signs situ. Further, performing TCGA data mining using patient samples, demonstrate positively correlated. Overall, our experimental indicate negative regulator loss sensitizes Therefore, small molecule inhibitors hold huge promise as novel therapeutics their potential can harnessed against apoptosis-resistant condition.

Language: Английский

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